Sign up to receive free email alerts when patent applications with chosen keywords are publishedSIGN UP

Abstract:

The invention relates generally to a probe interface method and apparatus
for use in conjunction with an optical based noninvasive analyzer. More
particularly, an algorithm controls a sample probe position and attitude
relative to a skin sample site before and/or during sampling. For
example, a sample probe head of a sample module is controlled by an
algorithm along the normal-to-skin-axis. Preferably, the sample probe
head is positioned in terms of 3-D location in the x-, y-, and z-axes and
is attitude orientated in terms of pitch, yaw, and roll. Further,
attitude of the probe head is preferably orientated prior to contact of
the sample probe head with the tissue sample using indicators, such as
non-contact distance feedback from capacitance sensor, contacting or
non-contacting optical sensors, and/or contact electrical sensors.

Claims:

1. A noninvasive spectroscopic analyzer An apparatus for analyte property
determination from a sample site of a body part, comprising:a sample
probe having a sample probe tip; anda controller for controlling attitude
of said sample probe tip relative to localized curvature of the sample
site.

2. The noninvasive spectroscopic analyzer of claim 1, wherein attitude of
said sample probe tip relative to the sample site is defined in terms of
an x-, y-, and z-axis coordinate system, wherein said x-axis is defined
along a length of said body part, wherein said y-axis is defined across
said body part, and wherein said z-axis is normal to a plane formed by
said x- and y-axes.

3. The noninvasive spectroscopic analyzer of claim 2, wherein said
controller controls said attitude of said sample probe tip along all of
said x-, y-, and z-axes.

4. The noninvasive spectroscopic analyzer of claim 2, wherein said
controller controls said attitude of said sample probe tip along a
normal-to-sample site axis, wherein said normal-to-sample site axis is
not said z-axis.

5. The noninvasive spectroscopic analyzer of claim 2, wherein said
attitude comprises a pitch and a roll, wherein said controller controls
said pitch and said roll of said sample probe tip relative to the sample
site, wherein pitch comprises rotation of said sample probe tip about
said y-axis, wherein roll comprises rotation of said sample probe tip
about said x-axis.

6. The noninvasive spectroscopic analyzer of claim 1, further
comprising:an input signal, said input signal providing said controller
with information about said attitude of said sample probe tip relative to
the sample site.

7. The noninvasive spectroscopic analyzer of claim 6, wherein said input
signal comprises a plurality of capacitance signals, wherein each of said
plurality of capacitance signals provides information on a distance
between a localized section of said sample probe tip and the sample site.

8. The noninvasive spectroscopic analyzer of claim 6, wherein said input
signal comprises a conductive contact signal, wherein said conductive
contact signal changes in current as an indication that proximate contact
between said sample probe tip and the sample site is established.

9. The noninvasive spectroscopic analyzer of claim 7, further
comprising:means for adjusting position of said sample probe tip relative
to the tissue site, wherein said controller first adjusts said pitch and
said roll of said sample probe tip and, thereafter, said means for
adjusting moves, said sample probe tip along a normal-to-skin axis,
wherein said normal-to-skin axis is not aligned with an axis
corresponding to that of a force attributable to gravity.

10. The noninvasive spectroscopic analyzer of claim 1, further
comprising:means for adjusting said attitude of said sample probe tip
relative to the tissue site in terms of a pitch and a roll.

11. The noninvasive spectroscopic analyzer of claim 10, wherein said means
for adjusting comprises:a first motor assembly operating through a pivot
point to move a first concentric ring to control pitch of said sample
probe tip;a second motor operating through a second pivot point to move a
second concentric ring to control roll of said sample probe tip.

12. The noninvasive spectroscopic analyzer of claim 1, further
comprising:a motor for controlling movement of said sample probe tip
along a normal-to-skin-axis, wherein said normal-to-skin axis is
tangential to a plane defined by said x- and y-axes and is not aligned
with an axis corresponding to that of a force attributable to gravity.

13. A method for analyte property determination from a sample site of a
body part, comprising the steps of:collecting a spectrum with a
noninvasive analyzer comprising:a sample probe having a sample probe tip;
anda controller; andcontrolling attitude of said sample probe tip with
said controller relative to localized curvature of the sample site.

14. The method of claim 13, further comprising the step of:positioning
said sample probe tip at an attitude relative to the sample site, wherein
said attitude is defined in terms of an x-, y-, and z-axis coordinate
system, wherein said x-axis is defined along the length of a body part,
wherein said y-axis is defined across said body part, wherein said z-axis
is normal to a plane formed by said x- and y-axes.

15. The method of claim 14, further comprising the step of:said controller
controlling attitude of said sample probe tip along all of said x-, y-,
and z-axes.

16. The method of claim 14, wherein said z-axis comprises a
normal-to-sample site axis, wherein said z-axis does not align with an
axis corresponding to that of a force attributable to gravity.

17. The method of claim 14, further comprising the step of:said controller
controlling a pitch and a roll of said sample probe tip relative to the
sample site, wherein pitch comprises rotation of said sample probe tip
about said y-axis, and wherein roll comprises rotation of said sample
probe tip about said x-axis.

18. The method of claim 13, further comprising the step of:an input signal
providing said controller with information about said attitude of said
sample probe tip relative to the sample site.

19. The method of claim 18,wherein said input signal comprises a plurality
of capacitance signals; andfurther comprising the step of each of said
plurality of capacitance signals providing information on a distance
between a localized section of said sample probe tip and the sample site.

20. The method of claim 18,wherein said input signal comprises a
conductive contact signal; andfurther comprising the step of said
conductive contact signal rising in current as an indication that
proximate contact between said sample probe tip and the sample site is
established.

21. The method of claim 19, further comprising the step of:adjusting
position of said sample probe tip relative to the tissue site, wherein
said controller first adjusts pitch and roll of said sample probe tip
and, thereafter, moved said sample probe tip along a normal-to-skin axis,
wherein said normal-to-skin axis is not aligned with an axis
corresponding to that of a force attributable to gravity.

22. The method of claim 13, further comprising the step of:adjusting said
attitude of said sample probe tip relative to the tissue site in terms of
a pitch and a roll.

23. The method of claim 22, wherein said step of adjusting further
comprises the steps of:a first motor assembly moving a first concentric
ring to control pitch of said sample probe tip; anda second motor moving
a second concentric ring to control roll of said sample probe tip.

24. The method of claim 23, further comprising the step of:a third motor
controlling movement of said sample probe tip along an axis that is
normal to said sample site axis, wherein said normal to skin said sample
site axis is not aligned with an axis corresponding to that of a force
attributable to gravity.

25. The method of claim 13, further comprising the step of:generating a
glucose concentration from said spectrum, wherein said spectrum comprises
signals at wavelengths from about 1200 to above 1800 nm.

[0006]The invention relates generally to measurement of analyte properties
in tissue. One embodiment relates to sample probe movement control in a
noninvasive measurement.

[0007]2. Discussion of the Related Art

[0008]Sampling deformable skin tissue with a spectrometer is complicated
by optical and mechanical mechanisms occurring before and/or during
sampling.

[0009]In a first case, a representative optical sample of an object is
collected without contacting the object with the spectrometer. In this
case, specular reflectance and stray light is of concern. In one
instance, mechano-optical methods are used to reduce the amount of
specularly reflected light collected. However, this is greatly
complicated by an object having a surface that diffusely scatters light.
In a second instance, an algorithm is used to reduce the effects of
specular reflectance. This is complicated by specularly reflected light
contributing in an additive manner to the resultant spectrum. The
additive contribution results in a nonlinear interference, which results
in a distortion of the spectrum that is difficult to remove. The problem
is greatly enhanced as the magnitude of the analyte signal decreases.
Thus, for low signal-to-noise ratio measurements, specularly reflected
light is preferably avoided. For example, noninvasively determining an
analyte property, such as glucose concentration, from a spectrum of the
body is complicated by additive specularly reflected light in the
collected spectrum. As the analyte signal decreases in magnitude, the
impact of specularly reflected light increases.

[0010]In a second case, a spectrum of an object is collected after
contacting the object with a spectrometer. For objects or samples that
are deformable, the optical properties of the sample are changed due to
contact of an optical probe with the sample, which deforms the sample and
results in changed optical properties of the sample. Changed optical
properties due to movement of a sample before or during sampling include:
[0011]absorbance; and [0012]scattering.

[0013]In this second case, the sampling method alters the sample, often
detrimentally. The changes in the sample resulting from the sampling
method degrade resulting sample interpretation. As the signal level of
the analyte decreases, the relative changes in the sample due to sampling
result in increasing difficulty in extraction of analyte signal. In some
instances, the sampling induced changes preclude precise and/or accurate
analyte property determination from a sample spectrum. For example, a
sample probe contacting skin of a human alters the sample. Changes to the
skin sample upon contact, during sampling, and/or before sampling
include: [0014]stretching of skin; [0015]compression of skin; and
[0016]altered spatial distribution of sample constituents.

[0017]Further, the changes are often time dependent and methodology of
sampling dependent. Typically, the degree of contact to the sample by the
spectrometer results in nonlinear changes to a resulting collected
spectrum.

[0018]Manually manipulating a spectrometer during the method of optical
sampling requires human interaction. Humans are limited in terms of
dexterity, precision, reproducibility, and sight. For example, placing a
spectrometer in contact with an object during sampling is complicated by
a number of parameters including any of: [0019]not being able to reach
and see the sample at the same time; [0020]the actual sampling area being
visually obscured by part of the spectrometer or sample; [0021]placing
the analyzer relative to the sample within precision and/or accuracy
specifications at, near, or beyond human control limits; and
[0022]repeatedly making a measurement due to human fatigue and frailty.

Noninvasive Technologies

[0023]There are a number of reports on noninvasive technologies. Some of
these relate to general instrumentation configurations, such as those
required for noninvasive glucose concentration estimation, while others
refer to sampling technologies. Those related to the present invention
are briefly reviewed here:

[0024]P. Rolfe, Investigating substances in a patient's bloodstream, U.K.
patent application ser. no. 2,033,575 (Aug. 24, 1979) describes an
apparatus for directing light into the body, detecting attenuated
backscattered light, and using the collected signal to determine glucose
concentrations in or near the bloodstream.

[0025]C. Dahne, D. Gross, Spectrophotometric method and apparatus for the
non-invasive, U.S. Pat. No. 4,655,225 (Apr. 7, 1987) describe a method
and apparatus for directing light into a patient's body, collecting
transmitted or backscattered light, and determining glucose
concentrations from selected near-infrared wavelength bands. Wavelengths
include 1560 to 1590, 1750 to 1780, 2085 to 2115, and 2255 to 2285 nm
with at least one additional reference signal from 1000 to 2700 nm.

[0027]M. Robinson., K. Ward, R. Eaton, D. Haaland, Method and apparatus
for determining the similarity of a biological analyte from a model
constructed from known biological fluids, U.S. Pat. No. 4,975,581 (Dec.
4, 1990) describe a method and apparatus for measuring a concentration of
a biological analyte, such as glucose concentration, using infrared
spectroscopy in conjunction with a multivariate model. The multivariate
model is constructed from a plurality of known biological fluid samples.

[0028]J. Hall, T. Cadell, Method and device for measuring concentration
levels of blood constituents non-invasively, U.S. Pat. No. 5,361,758
(Nov. 8, 1994) describe a noninvasive device and method for determining
analyte concentrations within a living subject using polychromatic light,
a wavelength separation device, and an array detector. The apparatus uses
a receptor shaped to accept a fingertip with means for blocking
extraneous light.

[0029]S. Malin, G Khalil, Method and apparatus for multi-spectral analysis
of organic blood analytes in noninvasive infrared spectroscopy, U.S. Pat.
No. 6,040,578 (Mar. 21, 2000) describe a method and apparatus for
determination of an organic blood analyte using multi-spectral analysis
in the near-infrared. A plurality of distinct nonoverlapping regions of
wavelengths are incident upon a sample surface, diffusely reflected
radiation is collected, and the analyte concentration is determined via
chemometric techniques.

Specular Reflectance

[0030]R. Messerschmidt, D. Sting Blocker device for eliminating specular
reflectance from a diffuse reflectance spectrum, U.S. Pat. No. 4,661,706
(Apr. 28, 1987) describe a reduction of specular reflectance by a
mechanical device. A blade-like device "skims" the specular light before
it impinges on the detector. A disadvantage of this system is that it
does not efficiently collect diffusely reflected light and the alignment
is problematic.

[0031]R. Messerschmidt, M. Robinson Diffuse reflectance monitoring
apparatus, U.S. Pat. No. 5,636,633 (Jun. 10, 1997) describe a specular
control device for diffuse reflectance spectroscopy using a group of
reflecting and open sections.

[0033]Malin, supra, describes the use of specularly reflected light in
regions of high water absorbance, such as 1450 and 1900 nm, to mark the
presence of outlier spectra wherein the specularly reflected light is not
sufficiently reduced.

[0034]K. Hazen, G. Acosta, A. Abul-Haj, R. Abul-Haj, Apparatus and method
for reproducibly modifying localized absorption and scattering
coefficients at a tissue measurement site during optical sampling, U.S.
Pat. No. 6,534,012 (Mar. 18, 2003) describe a mechanical device for
applying sufficient and reproducible contact of the apparatus to the
sampling medium to minimize specular reflectance. Further, the apparatus
allows for reproducible applied pressure to the sample site and
reproducible temperature at the sample site.

Temperature

[0035]K. Hazen, Glucose Determination in Biological Matrices Using
Near-Infrared Spectroscopy, doctoral dissertation, University of Iowa
(1995) describes the adverse effect of temperature on near-infrared based
glucose concentration estimations. Physiological constituents have
near-infrared absorbance spectra that are sensitive, in terms of
magnitude and location, to localized temperature and the sensitivity
impacts noninvasive glucose concentration estimation.

[0037]K. Hazen, G. Acosta, A. Abul-Haj, R. Abul-Haj, Apparatus and method
for reproducibly modifying localized absorption and scattering
coefficients at a tissue measurement site during optical sampling, U.S.
Pat. No. 6,534,012 (Mar. 18, 2003) describe in a first embodiment a
noninvasive glucose concentration estimation apparatus for either varying
the pressure applied to a sample site or maintaining a constant pressure
on a sample site in a controlled and reproducible manner by moving a
sample probe along the z-axis perpendicular to the sample site surface.
In an additional described embodiment, the arm sample site platform is
moved along the z-axis that is perpendicular to the plane defined by the
sample surface by raising or lowering the sample holder platform relative
to the analyzer probe tip. The '012 patent further teaches proper contact
to be the moment specularly reflected light is about zero at the water
bands about 1950 and 2500 nm.

Coupling Fluid

[0038]A number of sources describe coupling fluids with important sampling
parameters.

[0039]Index of refraction matching between the sampling apparatus and
sampled medium to enhance optical throughput is known. Glycerol is a
common index matching fluid for optics to skin.

[0042]T. Blank, G. Acosta, M. Mattu, S. Monfre, Fiber optic probe guide
placement guide, U.S. Pat. No. 6,415,167 (Jul. 2, 2002) describe a
coupling fluid of one or more perfluoro compounds where a quantity of the
coupling fluid is placed at an interface of the optical probe and
measurement site. Perfluoro compounds do not have the toxicity associated
with chlorofluorocarbons.

[0043]M. Makarewicz, M. Mattu, T. Blank, G. Acosta, E. Handy, W. Hay, T.
Stippick, B. Richie, Method and apparatus for minimizing spectral
interference due to within and between sample variations during in-situ
spectral sampling of tissue, U.S. patent application Ser. No. 09/954,856
(filed Sep. 17, 2001) describe a temperature and pressure controlled
sample interface. The means of pressure control are a set of supports for
the sample that control the natural position of the sample probe relative
to the sample.

Positioning

[0044]E. Ashibe, Measuring condition setting jig, measuring condition
setting method and biological measuring system, U.S. Pat. No. 6,381,489,
Apr. 30, 2002 describes a measurement condition setting fixture secured
to a measurement site, such as a living body, prior to measurement. At
time of measurement, a light irradiating section and light receiving
section of a measuring optical system are attached to the setting fixture
to attach the measurement site to the optical system.

[0045]J. Roper, D. Bocker, System and method for the determination of
tissue properties, U.S. Pat. No. 5,879,373 (Mar. 9, 1999) describe a
device for reproducibly attaching a measuring device to a tissue surface.

[0046]J. Griffith, P. Cooper, T. Barker, Method and apparatus for
non-invasive blood glucose sensing, U.S. Pat. No. 6,088,605 (Jul. 11,
2000) describe an analyzer with a patient forearm interface in which the
forearm of the patient is moved in an incremental manner along the
longitudinal axis of the patient's forearm. Spectra collected at
incremental distances are averaged to take into account variations in the
biological components of the skin. Between measurements rollers are used
to raise the arm, move the arm relative to the apparatus and lower the
arm by disengaging a solenoid causing the skin lifting mechanism to lower
the arm into a new contact with the sensor head.

[0047]T. Blank, G. Acosta, M. Mattu, S. Monfre, Fiber optic probe
placement guide, U.S. Pat. No. 6,415,167 (Jul. 2, 2002) describe a
coupling fluid and the use of a guide in conjunction with a noninvasive
glucose concentration analyzer in order to increase precision of the
location of the sampled tissue site resulting in increased accuracy and
precision in noninvasive glucose concentration estimations.

[0049]Clearly, there exists a need for controlling optical based sampling
methods to minimize collection of specularly reflected light, for
minimizing collection of stray light, to control the load applied by the
sample probe to the measurement site as a function of time, and for
minimizing sampling related changes to a deformable sample. For optical
sampling of a deformable object, it would be desirable to provide a
method and apparatus that automatically reduces the effects of
non-contact and excessive contact of the sample during sampling.

SUMMARY OF THE INVENTION

[0050]The invention relates generally to a probe interface method and
apparatus for use in conjunction with an optically based noninvasive
analyzer. More particularly, an algorithm controls a sample probe
position and attitude relative to a skin sample site during sampling.

BRIEF DESCRIPTION OF THE DRAWINGS

[0051]FIG. 1 illustrates an analyzer interfacing with a human body;

[0052]FIG. 2 illustrates a sample probe (A) moving along a z-axis and
(B-C) moving along a normal-to-skin-axis;

[0053]FIG. 3 illustrates a noninvasive analyzer including a base module, a
communication bundle, and a sample module that is controlled by an
algorithm, according to the invention;

[0063]FIG. 13 illustrates an attitude controller for a sample probe in a
non-tilt state;

[0064]FIG. 14 illustrates an attitude controller for a sample probe in a
pitched state; and

[0065]FIG. 15 illustrates an attitude controller for a sample probe in a
rolled state.

DETAILED DESCRIPTION OF THE INVENTION

[0066]The invention comprises a noninvasive analyzer sampling module.
Preferably the sample module controls position and/or attitude of a
sample probe tip relative to a sample site. Optionally, the sample probe
is controlled by an algorithm to minimally contact a sample site,
tangentially contact a sample site and/or to controllably displace a
tissue sample relative to the nominal plane of the sample tissue surface.

[0067]A key source of error in a noninvasive analyte property
determination, such as a glucose concentration determination, is related
to probe design and patient interface, as opposed to the spectrograph
unit or algorithm design. A key parameter to control is the applied force
or pressure applied by the sample probe to the interrogated tissue sample
site. A force and/or displacement controlled sample interface aids
generation of reproducible sample spectra used in conjunction with a
noninvasive analyzer and algorithm to create acceptable reproducibility.

[0068]Preferably, a tip of a sample probe head of a sample module is
controlled by an algorithm along a normal-to-skin-axis. Preferably, the
sample probe head is positioned in terms of 3-D location in the x-, y-,
and z-axes and is attitude orientated in terms of pitch, yaw, and roll.
Further, attitude of the probe head is preferably orientated prior to
contact of the sample probe head with the tissue sample using remote
indicators, such as feedback from capacitance, optical, or electrical
sensors.

[0069]Referring now to FIG. 1, an analyzer 10 is illustrated interfacing
with a human body. The analyzer, described infra, interfaces with any
skin surface of the human body.

Coordinate System

[0070]Herein, positioning and attitude are defined. Positioning is defined
using a x-, y-, and z-axes coordinate system relative to a given body
part. A relative x-, y-, z-axes coordinate system is used to define a
sample probe position relative to a sample site. The x-axis is defined
along the length of a body part and the y-axis is defined across the body
part. As an illustrative example using a sample site on the forearm, the
x-axis runs between the elbow and the wrist and the y-axis runs across
the axis of the forearm. Similarly, for a sample site on a digit of the
hand, the x-axis runs between the base and tip of the digit and the
y-axis runs across the digit. The z-axis is aligned with gravity and is
perpendicular to the plane defined by the x- and y-axis. Further, the
orientation of the sample probe relative to the sample site is defined in
terms of attitude. Attitude is the state of roll, yaw, and pitch. Roll is
rotation of a plane about the x-axis, pitch is rotation of a plane about
the y-axis, and yaw is the rotation of a plane about the z-axis. Tilt is
used to describe both roll and pitch.

Normal-to-Skin-Axis

[0071]Position and attitude describe the sample probe tip surface relative
to a sample site. Referring now to FIG. 2, both z-axis and
normal-to-skin-axis movement of a sample probe relative to a sample site
are illustrated. In FIG. 2A, a sample probe 13 having a sample probe tip
16 is illustrated relative to a skin sample 14. The skin sample 14 is
illustrated with a greatly magnified surface curvature for ease of
illustration and to emphasizing the importance of the localized curvature
of the skin sample 14 surface. The sample probe 13 is moved from a
position not in contact with the skin sample 14 as illustrated by the
solid line. As illustrated by the dashed line, the sample probe tip is
moved into contact with the sample 14 by moving the sample probe 14 along
the z-axis. In this case, where the sample probe has no tilt relative to
a sample point on the skin sample 14, the z-axis is also the
normal-to-skin-axis. In FIG. 2B, the sample probe 13 is tilted relative
to the sample point on the skin sample, where tilt is rotation of the
sample probe through at least one of roll and pitch. Comparing FIGS. 2B
and 2C, the sample probe 13 is observed to be brought to the skin sample
14 by moving the sample probe 13 along a normal-to-skin-axis. Notably,
the normal-to-skin axis for the sample probe for the sample 14
illustrated in FIGS. 2B and 2C is not the same as movement along the
z-axis as illustrated in FIG. 2A.

[0072]When the sample probe has tilt, movement of the sample probe along a
normal-to-skin-axis has advantages as opposed to moving the sample probe
along the z-axis. When the tilted sample is brought to the skin surface
along the normal-to-skin-axis, the sample probe interacts with the skin
with minimal energy. For example, shearing forces are minimized when the
sample probe is brought to the sample site along the normal-to-skin-axis.
In stark contrast, when the tilted sample probe is brought to the skin
surface along the z-axis, a shearing force is applied to the skin.
Similarly, the normal-to-skin-axis movement of the sample probe minimizes
stress and strain on the sample site. As discussed, supra, the reduction
of stress and strain on the sample site reduces spectrally observed
interferences that degraded optical analyte property estimation, such as
noninvasive glucose concentration determination. Further, movement of the
sample probe along the normal-to-skin axis results in: [0073]minimal
application of force to the sample site to achieve sample probe/tissue
sample contact; [0074]minimal displacement of the pliable tissue sample
when sample probe/tissue sample contact is achieved; and [0075]a
reduction or elimination of detected specularly reflected light off of
the skin sample site surface with sample probe/tissue sample contact is
achieved.

[0076]Preferably, the sample probe is brought to the sample site in terms
of position and attitude using automated sample probe movement.

Instrumentation

[0077]Referring now to FIG. 3, an analyzer is illustrated. The analyzer 10
includes at least a source, illumination optics, collection optics, a
detector, and an analysis algorithm. The analyzer 10 optionally includes
a base module 11, communication bundle 12, and sample module 13. The base
module has a display module. The analyzer components are optionally
separated into separate housing units or are integrated into a single
unit, such as a handheld unit. Preferably, a source is integrated into
either the base module or the sample module. In a first case, the source
element is integrated into the base module and the communication bundle
carries the incident optical energy to the sample. In a second preferred
case, the source element is integrated into the sample module. In both
cases, photons are directed toward the tissue sample via a sample probe
that is part of the sample module and the photonic signal collected from
the sample by the sampling module is carried to a detector, typically in
the base module, via the communication bundle. In an example of a
noninvasive glucose concentration analyzer, the analyzer detects signals
from a range of about 1100 to 1900 nm or about 1200 to 1800 nm.

[0078]Preferably, a signal processing means results in a control signal
that is transferred from the base module via the communication bundle
back to the sampling module. The communicated control signal is used to
control the movement, such a position and attitude of the sample probe
relative to the tissue sample or reference material.

Tissue Stress/Strain

[0079]The controller optionally moves the sample probe so as to make
minimal, proximate, and/or controlled contact with a sample to control
stress and/or strain on the tissue, which is often detrimental to a
noninvasive analyte property determination. Strain is the elongation of
material under load. Stress is a force that produces strain on a physical
body. Strain is the deformation of a physical body under the action of
applied force. In order for an elongated material to have strain there
must be resistance to stretching. For example, an elongated spring has
strain characterized by percent elongation, such as percent increase in
length.

[0080]Skin contains constituents, such as collagen, that have spring-like
properties. That is, elongation causes an increase in potential energy of
the skin. Strain induced stress changes optical properties of skin, such
as absorbance and scattering. Therefore, it is undesirable to make
optical spectroscopy measurements on skin with various stress states.
Stressed skin also causes fluid movements that are not reversible on a
short timescale. The most precise optical measurements would therefore be
conducted on skin in the natural strain state, such as minimally or
non-stretched stretched skin. Skin is stretched or elongated by applying
loads to skin along any of the x-, y-, and z-axes. Controlled contact
reduces stress and strain on the sample. Reducing stress and strain on
the sample results in more precise sampling and more accurate and precise
glucose concentration estimations.

[0081]An example of using light to measure a physical property, such as
contact, stress, and/or strain, in tissue is provided. Incident photons
are directed at a sample and a portion of the photons returning from the
sample are collected and detected. The detected photons are detected at
various times, such as when no stress is applied to the tissue and when
stress is applied to the tissue. For example, measurements are made when
a sample probe is not yet in contact with the tissue and at various times
when the sample probe is in contact with the tissue, such as immediately
upon contact and with varying displacement of the sample probe into the
tissue, such as within 0.5, 1, 2, 5, or 10 seconds from time of contact
of the sample probe with the tissue. The displacement into the tissue is
optionally at a controlled or variable rate. The collected light is used
to determine properties. One exemplary property is establishing contact
of the sample probe with the tissue. A second exemplary property is
strain. The inventors determined that different frequencies of light are
indicative of different forms of stress/strain. For example, in regions
of high water absorbance, such as about 1450 nm, the absorbance is
indicative of water movement. Additional regions, such as those about
1290 nm, are indicative of a dermal stretch. The time constant of the
response for water movement versus dermal stretch is not the same. The
more fluid water movement occurs approximately twenty percent faster than
the dermal stretch. The two time constants allow interpretation of the
tissue state from the resultant signal. For example, the interior or
subsurface hydration state is inferred from the signal. For example, a
ratio of responses at high absorbance regions and low absorbance regions,
such as about 1450 and 1290 nm, is made at one or more times during a
measurement period. Changes in the ratio are indicative of hydration.
Optionally, data collection routines are varied depending upon the
determined state of the tissue. For example, the probing tissue
displacement is varied with change in hydration. The strain measurement
is optionally made with either a targeting system or measurement system.
The tissue state probe describe herein is optionally used in conjunction
with a dynamic probe, described infra.

Actuator/Controller

[0082]A controller controls the movement of one or more sample probes of
the targeting and/or measuring system via one or more actuators. An
actuator moves the sample probe relative to the tissue sample. One or
more actuators are used to control the position and/or attitude of the
sample probe. The actuators preferably acquire feedback control signals
from the measurement site or analyzer. The controller optionally uses an
intelligent system for locating the sample site and/or for determining
surface morphology. Controlled elements include any of the x-, y-, and
z-axes positions of sampling along with pitch, yaw, and/or roll of the
sample probe. Also optionally controlled are periods of light launch,
intensity of light launch, depth of focus, and surface temperature.
Several examples signal generation used with the controller and actuator
follow.

[0083]In a first example, the controller hunts in the x- and y-axes for a
spectral signature.

[0084]In a second example, the controller moves a sample probe via the
actuator toward or away from the sample along the z-axis. The controller
optionally uses feedback from a targeting system, from the measurement
system, or from an outside sensor in a closed-loop mechanism for deciding
on targeting probe movement and for sample probe movement.

[0085]In a third example, the controller optimizes a multivariate
response, such as response due to chemical features or physical features.
Examples of chemical features include blood/tissue constituents, such as
water, protein, collagen, elastin, and fat. Examples of physical features
include temperature, pressure, and tissue strain. Combinations of
features are used to determine features, such as specular reflectance.
For example, specular reflectance is a physical feature optionally
measured with a chemical signature, such as water absorbance bands
centered at about 1450, 1900, or 2600 nm.

[0086]In a fourth example, the controller uses signals acquired from the
sample probe, such as capacitance sensors to determine distance between
the sample probe and the tissue sample. For instance, the distance or
relative distance between the sample probe tip and the sample site is
determined. Due to the inverse relationship between capacitance and
distance, the sensitivity to distance between the sample site and the
sample probe increases as the distance between the sample and probe
decreases. Using this metric, the sample probe is brought into close
proximity to the sample site without displacing the sample site.
Capacitance sensors, as used herein, are readily used to place the sample
probe tip with a distance of less than about 05, 0.3, and preferably 0.1
millimeter to the sample site. A plurality of capacitance sensors on the
sample probe head are used to determine distance of each portion of the
sample probe tip from the skin sample site. The attitude of the sample
probe head is adjusted so that the plane of the sample probe tip is
brought down the normal-to-skin axis in a manner that the center of the
sample probe tip contacts the sample site first. For instance, feedback
from multiple capacitive sensors place along the along x- and/or y-axes
is optionally used to adjust or control tilt of the sample probe tip.
Preferably, the attitude adjustment of the sample probe tip is performed
prior to the sample probe making contact with the skin tissue.
Capacitance sensors are further described in U.S. patent application Ser.
No. 11/625,752 filed Jan. 22, 2007, which is incorporated herein in its
entirety by this reference thereto.

[0087]In a fifth example, one or more contact sensors are used to
determine contact of the sample probe tip with the sample site.
Acceptable optical contact is ascertained on the basis of one or more
contact sensors, which surround or are in close proximity to the
detection optic. As the sample probe is placed in mechanical contact with
the skin tissue, a signal is generated by the contact sensor which
indicates a contact event. For example, a conductive contact is detected
when the signal changes from its mean level by an amount greater than two
times the standard deviation of the noise. An electrical contact sensor
provides a rise in current as an indication that proximate contact
between said sample probe tip and the sample site is established. Upon
initial contact with one section of a sample probe tip, a sample is
collected or the tip is backed off from the sample site and attitude
adjusted to be tangential to the center of the sample site. Contact
sensors are further described in U.S. provisional patent application No.
60/864,375 filed Nov. 3, 2006, which is incorporated herein in its
entirety by this reference thereto.

[0088]In a sixth example, the controller controls elements resulting in
pathlength and/or depth of penetration variation. For example, the
controller controls an adjustable iris in the sample probe for control of
radial spread of incident light, a rotating wheel, a focusable
backreflector, or an incident optic controlling position and angle of
incident light.

[0089]Preferably, two or more of the above described sensor response are
used cooperatively in controlling the sample probe position and/or
attitude of the analyzer relative to the sample. For example, the various
sensor systems are used in control of the motion of the sample probe at
different distances between a tip of the sample probe and the tissue
sample. In a particular example, a target/vision system is used to find a
tissue sample site to move the analyzer probe head toward, a capacitive
sensor system is used to orient the tilt of the probe head to nominally
match that of the skin surface at the sample site, the capacitive sensor
is further used in positioning the sample probe head close to the sample
site, and a conductive sensor system is used in fine positioning of the
tip of the sample probe headed to distances of less than a tenth of a
millimeter and preferably about a hundredth of a millimeter from the
tissue sample site.

[0090]The actuator/controller move the sample probe tip so that the
optical and physical effect of displacement of tissue by the sample probe
head prior to or during sampling is minimized.

Effect of Displacement on Tissue Spectra

[0091]In the following experiment, the effect on noninvasive spectra of
displacement of a sample probe on a tissue sample is demonstrated. A
movable sample probe contained in the sample module is presented in a
first position not in contact with the sample in time 1 of FIG. 4. In
this example, the sample probe is guided to the sample location with an
optional guide element described in T. Blank, G. Acosta, M. Mattu, S.
Monfre, Fiber optic probe guide placement guide, U.S. Pat. No. 6,415,167
(Jul. 2, 2002), which is herein incorporated in its entirety by
reference. The guide element is replaceably attached to the sample site.
The attachment of the guide to the sample site results in formation of a
meniscus of skin in the opening of the guide. The meniscus is typically a
convex bulge of tissue from the nominal plane of the skin tissue but is
flat or concave in some individuals such as older people or those with
less collagen density at the sample site. The size of the meniscus is
subject dependent, varies on a given subject from day-to-day, and varies
on a subject within a day. A series of spacers are placed on top of the
guide that sterically provide a stop to the sample probe as the sample
probe moves down the z-axis, perpendicular to the skin surface, toward
the tissue sample. As individual spacers are removed, the sample probe
initiates contact with the sample. Removal of additional spacers results
in probe displacement of the deformable tissue sample.

[0092]Spectra are collected with subsequent removal of the steric stops
described supra. The resulting single beam spectra from 1100 to 1930 nm
collected with a 1.2, 1.1, 1.0, 0.9, 0.8, and 0.7 mm spacer are presented
in FIG. 5A. It is the relative movement of the sample probe along the
z-axis relative to the tissue sample that is important as opposed to the
size of the spacers. The observed intensity decreases as spacers are
removed and contact followed by displacement of the tissue results. Two
dominant spectral features are observed: the light of the second overtone
region from 1100 to 1450 nm and the light of the first overtone region
from 1450 to 1900 nm. The decrease in light intensity in these regions is
due to chemical and physical effects including large water absorbance
bands at 1450 and 1930 nm described infra. The decrease in intensity at
1450 nm is further analyzed in FIG. 5B. The observed intensity of 0.116
volts with a 1.2 mm spacer indicates that the sample probe has not yet
made contact with the tissue sample. The large drop in observed intensity
with a decrease in sample probe height of 1/10th of a millimeter to
1.1 mm indicates that contact with the skin is established. This is
confirmed by observing that at all wavelengths the intensity decrease is
most significant with this single change in spacer height and indicates
that specularly reflected light is significantly reduced and that the
resulting spectra are now dominated by the absorbance and scattering
nature of the tissue sample. This pedestal effect is described in S.
Malin U.S. Pat. No. 6,040,578, supra, and is herein incorporated in its
entirety by reference. Subsequent removal of spacers results in a further
displacement of the tissue sample by the sample probe. Increasing
displacement of the tissue sample by the sample probe result in changes
in the observed intensity of spectral bands associated with chemical and
physical features.

[0093]The single beam spectra collected as a function of displacement of
the tissue sample are subsequently converted into absorbance spectra with
use of an intensity reference spectrum and are presented in FIG. 6. The
resulting absorbance spectra reveal chemical and physical features of the
sample. Two large water absorbance bands are observed centered at 1450
and 1930 nm. Smaller fat and protein absorbance bands are observed in the
first and second overtone spectral regions. Scattering effects are
observed throughout the spectrum but are most prevalent in the higher
energy region of the spectra. The sample collected with the 1.2 mm spacer
that resulted in insufficient contact of the sample probe with the tissue
sample results in artificially low absorbance across the spectrum due to
the collection of spectrally reflected light into the collection optics
of the sample probe. In order to enhance the chemical features observed
in the first and second overtone spectral windows, the spectra were first
smoothed across time and subsequently smoothed across wavelengths with a
Savitsky-Golay 13 point second derivative. The resulting spectra are
presented in FIG. 7. The second derivative reduces the scattering
characteristics and allow the observation of the chemical features. The
spectral minima observed at 1152, 1687, and 1720 nm are dominated by the
absorbance of water, protein, and fat, respectively.

[0094]The change in absorbance of the water, protein, and fat spectral
features is plotted as a function of displacement in FIG. 8. In this
example, the absorbance of all three chemical features is observed to
decrease with increasing displacement of the sample probe into the tissue
sample. The dependence of the absorbance of the individual chemical and
physical features as a function of tissue displacement is dependent upon
a range of factors. The factors include: the physical dimension of the
sample probe tip interfacing with the tissue sample, the dimension of the
aperture in the guide, the chemical composition of the tissue sample, the
rate of displacement of the sample probe into the tissue, and a
historesis effect of previous contact of an outside object on the sample
site.

[0095]The displacement of the tissue sample by the sample probe results in
compression of the sample site. The displacement results in a number of
changes including at least one of: a change in the localized water
concentration as fluid is displaced, a change in the localized
concentration of chemicals that are not displaced such as collagen, and a
correlated change in the localized scattering concentration. In addition,
physical features of the sample site are changed. These changes include
at least one of: a compression of the epidermal ridge, compression of the
dermal papilla, compression of blood capillaries, deformation of skin
collagen, and the relative movement of components embedded in skin.

[0096]In this example, chemical and physical changes are observed with
displacement of the sample probe into the tissue sample. Specific
chemical features at three wavelengths are described. However, the
displacement of tissue is demonstrated by this example to effect the
spectra over a wide range of wavelengths from 1100 to 1930 nm. Additional
spectral data shows these pressure effects to be present in at least the
infrared region extending out to 2500 nm. Further, the displacement
effects are described for a few particular chemical and physical
structures. The displacement of tissue also effects a number of
additional skin chemical, physical, and structural features presented in
FIG. 9.

PREFERRED EMBODIMENTS

[0097]In a preferred embodiment, the sample probe is a part of the sample
module and the sample probe is controlled by an algorithm along the
normal-to-skin-axis. Preferably, the sample probe head is positioned in
terms of 3-D location in the x-, y-, and z-axes and is attitude
orientated in terms of pitch, yaw, and roll.

[0098]A schematic presentation of the sample module is presented in FIG.
10. The sample module includes an actuator and a sample probe. The
actuator is driven by a controller. The controller sends the control
signal from the algorithm to the sample module actuator via a
communication bundle. The actuator subsequently moves the sample probe
relative to the tissue sample site. The sample probe is controlled along
the z-axis from a position of no contact, to a position of tissue sample
contact, and optionally to a position of minimal tissue sample
displacement. The sample probe is presented in FIG. 10 at a first and
second period of time with the first time period presenting the sample
probe when it is not in contact with the sample site. The second time
period presents the sample probe with minimal displacement of the sample
tissue.

[0099]In another embodiment of the invention, a mechanical system for
adjusting attitude is affixed to a sample module or sample probe.
Referring now to FIG. 11, a sample module is presented with the outside
cover removed for clarity. A reflector 1101 reflects light from a source
toward the sample. Heat from the source is dissipated through a heat sink
1102. In this example, three drive mechanisms are used. Each illustrated
drive mechanism contains a motor 1106, gear box 1107, and bushing in a
spline shaft 1108, though any drive means capable of adjusting roll,
pitch, or position along the normal-to-skin-axis is suitable. The first
motor assembly 1103 adjusts pitch, the second motor assembly 1104 adjusts
roll, and the third motor assembly 1105 moves the tip of the sample probe
along a normal-to-skin axis.

[0100]Referring now to FIG. 12, items of the assembly of FIG. 11 are
removed to further expose internal elements. The spline shaft internals
of the three motor assemblies 1103-1105 are illustrated. The pictured
design has three concentric rings 1106-1108 for controlling attitude,
though other mechanical systems are usable. Movement of the first motor
assembly 1103 operates through a pivot point 1113 to move the second
concentric ring 1107 to control pitch of the sample probe tip. Movement
of the second motor 1104 operates through a second pivot point 1114 to
move the third concentric ring 1108 to control roll of the sample probe
tip. Movement of the third motor 1105 controls movement of the sample
probe tip along the normal-to-skin-axis.

[0101]Also illustrated in FIG. 12 are a collection optic 1109, first
illumination optic 1110, and second illumination optic 1111. Within the
sample module, the collection optic is surrounded by a light barrier to
prevent source light from penetrating into the collection optic. For
example, within the sample probe a metal sheath surrounds the collection
fiber optic. The first optic 1110 operates as any of a longpass filter,
shortpass filter, or bandpass filter to remove spectral regions of
undesirable photons. For example, the first optic 1110 removes infrared
heat at wavelengths longer than about 1900 or 2500 nm. As a second
example, the first optic comprises silicon and removes light at
wavelengths shorter than about 1100 nm. The first optic does not contact
the skin sample 14. The second optic 1111 proximately contacts the skin
sample 14 during analyzer use. The second optic preferably contains a
hole through which the collection optic 1109 penetrates to make proximate
contact with the skin surface. The second optic 1111 mechanically
supports the tip of the collection optic 1109. Extending radially about
the collection optic 1109 is a spacer placed between the collection optic
1109 and the second optic 1111.

[0102]Tilt is illustrated in FIGS. 13-15. Referring now to FIG. 13, the
three concentric rings 1106-1108 of FIG. 12 are illustrated as a top down
view and as a side view when the system is in a state of no pitch or
roll. Referring now to FIG. 14, movement of the lead screw of the first
motor 1103 results in pitch of the second ring 1107 and third ring 1108
relative to the first concentric ring 1106. Referring now to FIG. 15,
movement of the lead screw of the second motor 1104 results in roll of
the third ring 1108 relative to the second concentric ring 1107.

[0103]In another embodiment, attitude control of the sample probe tip
relative to a curved sample site or tissue site in terms of roll, pitch,
and/or yaw is controlled using a set of linear drives in combination with
ball pivots and slides to alter attitude of a mounting plate. The linear
drives, or alternatively drive motors, can also be used to control motion
of the sample probe tip along a z-axis or an axis normal to the surface
of a tissue site.

Tissue Displacement Control

[0104]Displacement of the tissue sample by the sample probe results in
changes in noninvasive spectra. Displacement of the sample tissue is
related to pressure applied to the sample tissue. However, as the tissue
is deformed the return force applied by the tissue sample to the sample
probe varies. Therefore, it is preferable to discuss that sample/tissue
interaction in terms of displacement instead of pressure.

[0105]Displacement of the tissue sample by the sample probe is preferably
controlled between an insufficient and excessive displacement or
pressure. Insufficient contact of the sample probe with the tissue sample
is detrimental. The surface of the skin tends to be rough and irregular.
Insufficient contact results in a surface reflection. Contact between the
sample probe and the tissue sample minimizes air pockets and reduces
optical interface reflections that contain no useful information. Contact
pressure must be high enough to provide good optical transmission of
source illumination into the capillary layer where the analytical signal
exists while minimizing reflections from the surface of the skin that
manifest as noise. Excessive displacement of the tissue sample by the
sample probe is detrimental. The primary region of interest for
measurement of blood borne analytes is the capillary bed of the dermis
region, which is approximately 0.1 to 0.4 mm beneath the surface. The
capillary bed is a compressible region and is sensitive to pressure,
torque, and deformation effects. The accurate representation of blood
borne analytes that are used by the body through time, such as glucose,
relies on the transport of blood to and from the capillary bed, so it is
not preferable to restrict this fluid movement. Therefore, contact
pressure should not be so high as to excessively restrict or to partially
restrict for an extended period of time flow of blood and interstitial
fluids to the sampled tissue region.

[0106]In the foregoing discussion, the preferred embodiment of the
invention is for the determination of a glucose concentration. Additional
analytes for concentration or threshold determination are those found in
the body including: water, protein, fat and/or lipids, blood urea
nitrogen (BUN), both therapeutic and illicit drugs, and alcohol.

[0107]Those skilled in the art will recognize that the present invention
may be manifested in a variety of forms other than the specific
embodiments described and contemplated herein. Departures in form and
detail may be made without departing from the spirit and scope of the
present invention. Accordingly, the invention should only be limited by
the Claims included below.